Recent patent on co...
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Recent patent on combination of antagonists of dopamine receptors, glycolysis inhibitor, and a cholesterol lowering agent to inhibit the growth of pancreatic cancer

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The patent application was done by two important institutions active in the field of cancer research:

Deutsches Krebsforschungszentrum Stiftung des Öffentlichen Rechts (Heidelberg, DE)
The Royal Institution for the Advancement of Learning/McGill University (Montreal, CA)

The patent suggests that the combination of

- dopamine receptor antagonists D2 (DRD2) such as pimozide, haloperidol,
- glycolisis (fermentation) inhibitors such as 2DG or 3BP and
- cholesterol inhibitors such as Atorvastatin

The concept is the following:

- Treatment with antipsychotic drugs, such as pimozide or haloperidol, induce ER-stress. 
- ER stress triggers a gene regulatory program, which is characterized by overexpression of genes encoding enzymes involved in glycolysis and lipogenesis
- Therefore, this leads to glycolytic activity as well as increased phospholipid turnover and cholesterol levels in cancer cells under ER-stress conditions
- Specifically, glycolysis and cholesterol biosynthesis pathways, which are activated by DRD2 antagonists, are used by cancer cells to survive the excessive ER stress induced by DRD2 antagonists
- As a result, combination of dopamine receptor antagonists D2 (DRD2), with glycolisis inhibitor 2DG and  cholesterol biosynthesis inhibitor Atorvastatin reduced tumor development.

So the key anti-cancer mechanisms here is the ER-stress. Actually, 2DG also induces ER stress.

Note that the ER-stress-driven glycolysis and alterations in cholesterol homeostasis have been linked to chemoresistance in cancer cells

Combined therapeutic approach for pimozide, gemcitabine, 2-DG and Atorvastin resulted in complete arrest of tumor growth.

Here is the patent

I previously discussed the glycolisis inhibitor 2DG here but if this is used in order to be effective it has to be taken metronomic

Other glycolisis inhibitors were discussed here

Statins such as Atorvastatin were discussed here


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